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【编译】运动元神经疾病的机制
原题：Dynein mutations impair autophagic clearance of aggregate-prone proteins
作者：Brinda Ravikumar1, 4, Abraham Acevedo-Arozena2, 4, Sara Imarisio1, 3, Zdenek Berger1, 3, Coralie Vacher1, Cahir J O'Kane3, Steve D M Brown2 & David C Rubinsztein1
单位：1 Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2XY, UK.2 Medical Research Council Mammalian Genetics Unit, Harwell, Oxfordshire, UK.
3 Department of Genetics, University of Cambridge, CB2 3EH, UK.4 These authors contributed equally to this work.
摘要：Mutations that affect the dynein motor machinery are sufficient to cause motor neuron disease. It is not known why there are aggregates or inclusions in affected tissues in mice with such mutations and in most forms of human motor neuron disease. Here we identify a new mechanism of inclusion formation by showing that decreased dynein function impairs autophagic clearance of aggregate-prone proteins. We show that mutations of the dynein machinery enhanced the toxicity of the mutation that causes Huntington disease in fly and mouse models. Furthermore, loss of dynein function resulted in premature aggregate formation by mutant huntingtin and increased levels of the autophagosome marker LC3-II in both cell culture and mouse models, compatible with impaired autophagosome-lysosome fusion.
译文：动力蛋白突变产生的效应足以造成运动神经元疾病的发生。但具体的影响机制在动物体内未被证实。我们的研究论文报告了运动元神经疾病的一种新机制，这种机制可能与更广泛的几种成人发生型神经退化性疾病有关，如肌萎缩性侧索硬化症、亨延顿症、帕金森氏症和阿尔氏海默氏症等。动力蛋白是与神经细胞中的传输器相关的一种分子。以前的研究显示，负责编码动力蛋白的基因中的变异会导致运动神经元疾病。我们研究表明，动力蛋白功能的降低会损害对受侵害神经元中的蛋白质聚集体的清除力。这种蛋白质聚集是几种神经退化性疾病中的常见特征，它们可能会毒化细胞。据推测，动力蛋白在正常情况下负责将清除聚集物的蛋白质复合体运送到神经元中恰当的位置。 [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-03-26 17:14
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